ABSTRACT Screen time is a major risk factor for childhood obesity and inadequate physical activity, both of which are determinants of type 2 diabetes (T2D), cardiovascular disease, and multiple cancers. Latinos are the largest and fastest growing minority in the US. Because US Latino children have more screen time and higher rates of obesity than their non-Latino White peers, interventions to reduce screen time adapted for Latino preschoolers are necessary to reduce health inequities related to obesity and T2D in the US. However, a systematic review reported no successful screen time reduction interventions among Latino preschoolers. Our team's pilot study tested the culturally adapted Fit 5 Kids screen time reduction curriculum among Latino preschoolers in Head Start. This short term cluster randomized controlled trial (RCT) is the only successful screen time reduction program for Latino preschoolers, having significantly reduced screen time by over 25 minutes/day. Our culturally adapted, multi-level intervention consists of lessons taught by study staff directly to preschoolers during Head Start, a weekly parent newsletter, child-tailored goal setting with parents, a lending library (books, games, arts/crafts, etc.) and parenting tips via text messages several times/week. We will use a social ecological model and consider multiple levels of influences for analyses: (1) individual-level influences, e.g., acculturation and social cognitive theory, (2) families, e.g., screen time parenting practices, (3) schools, and (4) macro-environmental influences, e.g., neighborhood disorder. Building on this pilot work, we propose a long term, efficacy, cluster RCT of the culturally adapted Fit 5 Kids among Latino preschoolers in Head Start from three US settings: Seattle, Houston, and the rural Central Valley of Washington State. Among 280 Latino 3-5 year olds at 20 Head Start centers, our Specific Aims (SA) and Hypotheses (H) include: SA1) To conduct a cluster RCT of the culturally adapted Fit 5 Kids curriculum to evaluate its efficacy in reducing screen time and excessive weight gain over a school year (8-months) H1) Fit 5 Kids will decrease children's screen time (primary outcome), BMI z-scores and dietary energy intake, and increase MVPA compared to controls SA2) To examine mediators and moderators associated with reducing Latino preschoolers' screen time H2) Parents' outcome expectations, self-efficacy, and screen time parenting practices will mediate the relationship between Fit 5 Kids and changes to preschoolers' screen time H3) Parents' depressive symptoms, stress, and social support will moderate changes to child screen time The proposed Fit 5 Kids cluster RCT will confirm the pilot's promising results, and the larger sample will allow for mediation analyses to better understand mechanisms. This research will provide justification for a future community effectiveness trial with implementation by Head Start teachers, and the eventual widespread dissemination of Fit 5 Kids in Head Start centers nationally.